Eight volunteers were exposed to trichloroethylene vapour (1,042 ,ug./l.) for five hours; 51 to 64% of the inhaled trichloroethylene was retained. The concentration of trichloroethanol and trichloroacetic acid in the urine was studied daily for a three-week period; on the third day both metabolites were determined in faeces, sweat, and saliva. The concentration of trichloroacetic acid in plasma and red blood cells was studied on alternate days. Of the trichloroethylene retained, 38-0 to 49 7 % was excreted in the urine as trichloroethanol and 27-4 to 35-7 % as trichloroacetic acid. Of both metabolites 8-4 % was excreted in the faeces. Sweat collected on the third day of the experiment contained 0 10 to 1P92 mg./100 ml. trichloroethanol and 0 15 to 0 35 mg./100 ml. trichloroacetic acid. In saliva the concentrations were 0 09 to 0-32 mg./100 ml. trichloroethanol and 0-10 to 0 15 mg./100 ml. trichloroacetic acid. The value of the expression trichloroethanol/ trichloroacetic acid calculated in the urine within 22 days was within the range 1-15 to 1-81.The importance of trichloroethylene to industry and the frequent occurrence of acute and chronic poisoning by this solvent led to the following studies in animals and man.It is well known that those exposed to trichloroethylene (TRI) excrete an insignificant amount of free TRI, a greater amount of monochloroacetic acid, and a considerable amount of trichloroethanol (TCE) and trichloroacetic acid (TCA) in the urine.Opinions on the mechanism of the toxic effect of TRI vary considerably. It is not yet known which metabolite is responsible for its toxicity. Comparison of LD50 in animals shows the order of toxicity to be: (1) Monochloroacetic acid (inhibitor of different enzyme systems); (2) TCE (powerful narcotic); (3) free TRI, and (4) TCA which is one order less toxic than TCE.Much work has been done on the excretion of TCE and TCA. Free TRI has been repeatedly determined in expired air. Little is known of TRI metabolism in man. Studies on the metabolites of TRI in plasma and blood cells have not been extensive. Little is known of other possible means of excretion, e.g. faeces. Sweat, saliva, and tears have not been studied hitherto. Although the amount of TRI metabolites excreted by routes other than the urine may be considered negligible, to us this small amount was found significant in accounting for that percentage of TRI for which there was no satisfactory explanation in our balance experiments. Analyses, therefore, of blood, sweat, saliva, and faeces, in addition to urine and expired air, in subjects exposed to a single inhalation of TRI in an exposure chamber were undertaken. Preparatory to this study experiments were carried out on the quantitative conditions for excretion of both the main metabolites of TRI in rabbit urine and a simultaneous comparison of the different metabolic balance in rabbits and man (Bartonicek and Soucek, 1959). MethodsApparatus.-The exposure chamber consisted of a brick-built room 91 m.3 hermetically sealed by a double door and ventilate...
The amounts of trichloroethanol and trichloroacetic acid excreted in the urine of four subjects who inhaled trichloroethylene in a concentration of about 1 mg./l. for a period of five hours in a laboratory experiment were determined. This experiment was repeated under the same conditions after tetraethyl thiuram disulphide (disulfiram) had been given in divided doses, totalling 3 or 3-5 g. The elimination of trichloroethanol in urine was decreased by 40 to 64%, and of trichloroacetic acid by 72 to 87%. The trichloroethylene excreted by the lungs in two of the subjects increased up to 65% of that retained within five hours. It is concluded that tetraethyl thiuram disulphide (disulfiram) strikingly inhibits the oxidation of trichloroethylene.The possible therapeutic use of this substance in cases of severe peroral trichloroethylene intoxication is discussed.In considering the toxicity of trichloroethylene (TRI) it is necessary to bear in mind the effect both of the whole molecule and that of its main metabolite trichloroethanol (TCE). Since TRI itself is very rapidly eliminated from the organism through the lungs we believe that the protracted narcotic effect of TRI is due to the TCE which is formed and which is eliminated rather slowly. This belief is supported by clinical observations of acute intoxication (Pierovska, Srbova', and Styblova, 1958). The conversion of TRI to TCE cannot therefore be considered as detoxication since the metabolite is more toxic (Soucek and Vlachova', 1960;Mikiskova and Mikiska, 1960). TCE probably only loses its narcotic properties after conjugation with glucuronic acid (Butler, 1949a). The next metabolite, trichloroacetic acid (TCA), described for the first time in dog urine by Barrett and Johnston (1939), can be considered non-toxic in the amount eliminated during intoxication with TRI. Theoretically the production of chloral, which was assumed by Butler (1949a), should be taken into consideration, but this has not been convincingly substantiated up to the present. Scansetti, Rubino, and Trompeo (1959) have recently described its presence in the human organism, but the methods used and the interpretation of results cannot, in our opinion, be accepted without reserve. In recent years Soucek and Vlachova have described other metabolites, namely monochloro-acetic acid (1954) and chloroform (1955). The production of these substances has not been confirmed by other authors.In the belief that TCE is the toxic metabolite of TRI, one of us (Bartonicek, 1962) tried to influence the oxidation of TRI into TCE. In laboratory experiments on man he showed that sodium lactate and fructose, administered intravenously, significantly decreased the amount of TCE eliminated in urine; fructose also significantly increased the amount of TCA eliminated. Thus he suggested that these substances be administered in TRI intoxication.Forssman, Owe-Larsson, and Skog (1955) reported that tetraethyl thiuram disulphide (disulfiram) greatly reduced the excretion of TCA in urine after the administration of TRI or ...
Rabbits were given trichloroethylene parenterally in a subacute trial lasting for 29 days and in a chronic trial lasting from 41 to 247 days. Behaviour, body weight and sedimentation rate were followed. The rabbits were killed at different times during the trial and the brains examined histologically and histochemically for any pathological changes. Moderate changes in the form of diffuse chronic‐ischaemic or toxic nerve cell damage in the majority of the cranial nerve nuclei, in the Gasserian ganglion, the cerebellar cortex were demonstrated as well as increased neuronal acid phosphatase activity. However, no severe neurological disturbances and no changes in the sedimentation rate were noted. The clinically known neurological and/or psychic derangements in humans are discussed in relation to the present pathological findings in rabbits.
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